Ontogeny of B cells and pathogenesis of humoral immunodeficiencies.

Studies of B-cell ontogeny have played an important role in furthering our understanding of the pathogenesis of immunodeficiencies. Development of clonal diversity for both T and B cells begins during the first trimester and is far advanced by midgestation. Fetal and neonatal B cells have a limited capacity to express IgG and IgA antibody responses, although precursors expressing these immunoglobulin classes are present. T-and B-cell interactions in the neonate are dominated by suppression. T helper cells are present and functional, but their capacity to drive IgG and IgA responses is impaired. This paper will review the major steps in ontogenetic development of B cells and the functions associated with each differentiation stage. Possible pathogenetic mechanisms of several humoral immunodeficiency diseases are reviewed from the perspective of the normal progression of B-cell differentiation.